Cited 21 times since 2007 (1.2 per year) source: EuropePMC Journal of hypertension, Volume 25, Issue 12, 1 1 2007, Pages 2454-2462 Olmesartan and pravastatin additively reduce development of atherosclerosis in APOE*3Leiden transgenic mice. van der Hoorn JW, Kleemann R, Havekes LM, Kooistra T, Princen HM, Jukema JW
Aim
This study was designed to investigate the effect of the angiotensin II receptor blocker olmesartan alone, or in combination with standard treatment with a statin, pravastatin, on atherosclerosis development in APOE*3Leiden transgenic mice.
Methods and results
Four groups of 15 mice received an atherogenic diet alone (plasma cholesterol 17.4 +/- 2.7 mmol/l) or supplemented with either 0.008% (w/w) olmesartan (9.3 mg/kg per day) (plasma cholesterol 16.4 +/- 3.9 mmol/l), 0.03% (w/w) pravastatin (35 mg/kg per day) (plasma cholesterol 14.6 +/- 2.6 mmol/l), or the combination of both (plasma cholesterol 14.5 +/- 2.9 mmol/l) for 6 months. Treatment with olmesartan or pravastatin reduced the development of atherosclerosis as compared to the control group (-46 and -39%, respectively). Pravastatin also reduced the severity of the lesions. As compared to control the combination of both treatments almost fully prevented atherosclerosis (-91%, P < 0.001) and strongly reduced lesion number (-69%), lesion severity (-79%), number of macrophages (-89%) and T lymphocytes (-86%) per cross-section. Treatment with olmesartan alone and in combination with pravastatin inhibited the adhesion of monocytes to the vessel wall (-22%; P < 0.05 and -25%; P < 0.01, respectively), and reduced the relative quantity of macrophages in the lesions (-38%; P < 0.05 and -26%; NS, respectively) as compared to control.
Conclusion
Olmesartan reduced atherosclerosis development mainly by decreasing monocyte adhesion and the relative amount of macrophages, whereas pravastatin inhibited the progression of atherosclerosis to more advanced lesions, reflecting different anti-atherosclerotic modes of action of the two drugs. Combination therapy with olmesartan and pravastatin additively reduced atherosclerosis development, resulting in less and less severe lesions.
